Abstract 184P
Background
FMPV-1 is a novel injectable vaccine to generate anti-cancer T cell responses. The vaccine is an immunogenic frameshift mutated transforming growth factor β receptor 2 (TGFβR2) peptide commonly occurring in microsatellite instability cancers (MSI-H). FMPV-1 is administered in combination with the adjuvant granulocyte macrophage colony stimulating factor (GM-CSF). This is the first clinical study to assess the safety and immunogenicity of FMPV-1/GM-CSF in man.
Methods
This was a single centre, open-label study in 16 healthy male subjects. Primary safety endpoints were adverse events (AEs), laboratory tests, vital signs, electrocardiograms (ECGs) and physical examination. Immunogenicity was assessed by FMPV-1-specific delayed type hypersensitivity (DTH) responses and FMPV-1-specific T-cell proliferation. All subjects received FMPV-1 (0.15 mg/injection) plus GM-CSF (0.03 mg/injection) as two separate injections on days 1, 8, 15, 29, and 43. DTH skin reactivity test was performed with FMPV-1 only on days 1, 29 & 43 with DTH response assessment 2 days later. T cell analyses were performed. Subjects were followed to Day 80 with further immunogenicity to be assessed at 6 and 12 months.
Results
16 subjects were enrolled and completed day 80 per protocol. FMPV-1/GM-CSF was well tolerated with no dose limiting toxicities reported, no major protocol deviations and no serious adverse events. Of the 17 treatment-emergent AEs occurring in 11 subjects, all were Grade 1 except 1 unrelated to IMP Grade 2 rise of creatine kinase. Six related AEs occurred in 6 subjects, being Grade 1 pruritus at injection site. No other clinically significant changes to ECG, vital signs or laboratory measures were seen. All subjects were DTH negative at baseline before dosing; after 3 FMPV-1/GM-CSF vaccinations, 8/16 (50%) subjects were positive at Day 31 with 15/16 (94%) at Day 45 after 4 vaccinations. In vitro T cell proliferation post-vaccination increased compared to pre-vaccination in subjects tested, with analysis ongoing.
Conclusions
The excellent safety profile of FMPV-1/GM-CSF and vaccine-specific immune responses in healthy subjects support further clinical development in a patient population for a phase 2 study in MSI-high colorectal cancer.
Clinical trial identification
NCT05238558.
Legal entity responsible for the study
Hubro Therapeutics AS.
Funding
Hubro Therapeutics AS.
Disclosure
N. Singh: Other, Institutional, Principal Investigator: Quotient Sciences. R.M. Miller: Financial Interests, Institutional, Full or part-time Employment: Hubro Therapeutics AS. S.J. Arbe-Barnes: Financial Interests, Institutional, Full or part-time Employment: Hubro Therapeutics AS. H. Kvalheim Eriksen: Financial Interests, Institutional, Full or part-time Employment, Stock options: Hubro Therapeutics AS. B. Iverson: Financial Interests, Institutional, Full or part-time Employment: Hubro Therapeutics AS; Financial Interests, Personal, Stocks/Shares: Hubro Therapeutics AS. J.A. Eriksen: Financial Interests, Personal and Institutional, Ownership Interest: Hubro Therapeutics AS; Financial Interests, Personal and Institutional, Stocks/Shares: Hubro Therapeutics AS; Financial Interests, Institutional, Full or part-time Employment: Hubro Therapeutics AS. All other authors have declared no conflicts of interest.